The objectives of the proposed work are as follows: (1) To study the regulation of the activity of alpha-isopropylmalate synthase of yeast. This will include the characterization of feedback-resistant mutants and further work on the mechanism and the physiological significance of the inactivation of this enzyme by CoA. (2) To study the regulation of enzyme synthesis in the leucine biosynthetic pathway of yeast. Emphasis will be on the problem of coordinate control of two unlinked genes, LEU1 and LEU2. The expression of both is strongly impaired by the simultaneous presence of leucine and throenine. (3) To further investigate the mechanism by which alpha-isopropylmalate synthase is incorporated into yeast mitochondria after it has been synthesized in the cytoplasm.